title: Anti-Pseudomonas aeruginosa serotype O11 LPS immunoglobulin M monoclonal antibody panobacumab (KBPA101) confers protection in a murine model of acute lung infection.
abstract: OBJECTIVE
  To investigate the in vivo efficacy in a murine pulmonary infection model of panobacumab (KBPA101), a human IgM monoclonal antibody directed against the O-polysaccharide moiety of Pseudomonas aeruginosa serotype O11, and to describe the anti-inflammatory effects in the lung as a consequence of the treatment.
  
  
  METHODS
  We established an experimental murine model of acute pneumonia by intranasal administration of P. aeruginosa serotype O11. Mice were treated, after infection, with a single intravenous injection of panobacumab and panobacumab lung bioavailability was assessed. Inflammatory parameters such as pro-inflammatory cytokine production and neutrophil recruitment in broncho-alveolar lavage fluid (BALF) were measured and bacterial load in the lung was analysed.
  
  
  RESULTS
  Panobacumab plays a significant role in addition to the host innate immune response, leading to improved control of pulmonary infection. The IgM antibody is able to reach the broncho-alveolar space and reduce the pulmonary bacterial load as well as lung inflammation in a dose-dependent manner. Furthermore, panobacumab treatment leads to enhanced neutrophil recruitment in BALF while reducing the host-derived production of pro-inflammatory mediators and lung injury.
  
  
  CONCLUSIONS
  These data provide evidence that panobacumab, an IgM-based immunotherapeutic, is highly efficacious in controlling acute lung infection by enhancing the natural innate immune response.
authors.affiliation: UMR6218, CNRS, Orléans, France.
authors.forename: T
authors.initials: T
authors.lastname: Secher
authors.forename: L
authors.initials: L
authors.lastname: Fauconnier
authors.forename: A
authors.initials: A
authors.lastname: Szade
authors.forename: O
authors.initials: O
authors.lastname: Rutschi
authors.forename: S C
authors.initials: SC
authors.lastname: Fas
authors.forename: B
authors.initials: B
authors.lastname: Ryffel
authors.forename: M P
authors.initials: MP
authors.lastname: Rudolf
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D005260:Female; D007075:Immunoglobulin M / Q000008:administration & dosage*; D007167:Immunotherapy / Q000379:methods*; D007275:Injections, Intravenous; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018410:Pneumonia, Bacterial / Q000188:drug therapy*; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000276:immunology* / Q000472:pathogenicity; D016896:Treatment Outcome
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D007075:Immunoglobulin M